The initial characterization of oncofetal antigen/immature laminin receptor protein (OFA/iLRP) was done by three independent groups, which studied oncofetal antigen or laminin receptor [1-3]. OFA/iLRP is a highly conserved protein that is over-expressed in a range of different cancers and has a dual function as ribosomal protein p40 [4-27]. The OFA/iLRP protein is comprised of a single polypeptide chain of 295 amino acids and has a molecular weight of about 37-44 kDa. The structure of OFA/iLRP has recently been elucidated to 2.15 Å [28]. The mature form of the laminin receptor (LRP) appears to be a dimer of acetylated OFA/iLRP, with a molecular weight of 67 kDa. The structure showed that the region between amino acids 112 to 140 of OFA/iLRP is involved in dimerization [28] of OFA/iLRP for forming the LRP. Although the 67 kDa LRP is on many normal cells as well as on tumor cells, there appears to be a preferential expression of the OFA/iLRP by fetal and tumor cells. Thus, the expression pattern makes OFA/iLRP a possible candidate protein to sensitize the immune system for the treatment of cancer and other diseases [6]. Antibodies specific for OFA/iLRP may also be used for the detection, diagnosis, and treatment of diseases known to be related to OFA/iLRP mis-expression.
The initial work on OFA/iLRP antibodies falls under two separate fields, the oncofetal antigen or the laminin receptor sides. The initial report of monoclonal antibodies against OFA/iLRP was found the same year for both the embryonic/fetal antigen and the laminin receptor [29, 30]. The antibodies developed against embryonic or fetal antigen reacted with a 44 kDa protein under denaturing conditions [30]. Antibodies previously developed against the laminin receptor had different biological activities based on the location of antibody binding [29]. One region that had biological activity of blocking laminin binding was recognized by monoclonal IgM antibody. The epitope that the monoclonal IgM antibody recognized was TEDWSAQPATEDWSA (SEQ. ID. NO.: 1) [26]. Studies on the 44 kDa OFA showed that the IgM monoclonal antibody (MAb 115) can be used for western blots, flow cytometry, and possibly oncogenicity testing [31]. However, since this antibody was not designed specifically against the OFA|OFA dimerization region, it reacts with both OFA/iLRP and LRP [31]. This monoclonal antibody was used for immunohistochemistry and protein purification of the OFA/iLRP or LRP [12, 32]. A different antibody was developed from peptides that detected the 67 kDa laminin receptor and showed increased laminin receptor expression in breast cancer [5,33]. Several published manuscripts describe the use of OFA/iLRP antibodies, while looking for autoimmune antibodies [6, 9, 10, 16, 19, 20, 25, 27, 34-36].
Since OFA/iLRP is associated with a range of different diseases, there is a need to develop diagnostic and clinical antibody applications. To date, there have been only a few attempts to develop a targeted antibody using peptides and this has been limited to one published report [5]. The region used in the published report produced antibodies that was reported to react with both the OFA/iLRP and laminin receptor [5,25]. Thus, a need exists to develop antibodies that are specific to OFA/iLRP, which can be used alone or in conjunction with other antibodies, to develop a range of different clinical, diagnostic, and/or veterinary applications. The development of antibodies in pairs, one that can recognize OFA/iLRP and one that can recognize both OFA/iLRP and LRP, allows for the development of several tests that can be use to treat, diagnosis or act as a reagent in OFA/iLRP diseases in all species due to the conserved nature of the protein.